Effect of fatty acids and their acyl-CoA esters on protein kinase C activity in fibroblasts: possible implications in fatty acid oxidation defects

Biochim Biophys Acta. 1994 Mar 10;1221(1):66-72. doi: 10.1016/0167-4889(94)90217-8.


We studied the effect of fatty acids and their acyl-CoA esters on protein kinase C (PK-C) activity in human skin fibroblasts. Butyrate, octanoate, palmitate and oleate did not alter PK-C activity in either cytosolic or particulate fraction. In the presence of calcium, phosphatidylserine and diacylglycerol, both palmitoyl-CoA (Pal-CoA) and oleoyl-CoA (Ole-CoA) enhanced particulate PK-C activity by approx. 70% and octanoyl-CoA (Oct-CoA) by approx. 35%. Partially purified cytosolic PK-C activity was enhanced by 60-70% by 13.5 microM of either Pal-CoA or Ole-CoA. Basal histone phosphorylation (i.e., PK-C-independent phosphorylation) was decreased in the particulate fraction in the presence of these esters in a concentration-dependent manner. Both Pal-CoA and Ole-CoA fully substituted diacylglycerol in activating the kinase in both the cytosolic and particulate fractions, whereas Oct-CoA had a moderate effect. The pattern of endogenous cytosolic and particulate protein phosphorylation was altered in the presence of either Pal-CoA or Ole-CoA. We conclude that long-chain fatty acyl-CoA esters may activate PK-C in non-stimulated fibroblasts, i.e., in the absence of physiological diacylglycerol formation. Activation of PK-C in stimulated fibroblasts, i.e., in the presence of an elevated diacylglycerol concentration, is less pronounced. These results support the hypothesis that activation of PK-C and alteration of endogenous protein phosphorylation may play a role in the pathogenesis of diseases in which there is intracellular accumulation of fatty acyl-CoA esters, such as in inborn fatty-acid oxidation defects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyl Coenzyme A / pharmacology*
  • Analysis of Variance
  • Calcium / pharmacology
  • Cells, Cultured
  • Cytosol / enzymology
  • Diglycerides / pharmacology
  • Fatty Acids, Nonesterified / pharmacology*
  • Fibroblasts / drug effects
  • Fibroblasts / enzymology
  • Humans
  • Kinetics
  • Phosphatidylserines / pharmacology
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Protein Kinase C / isolation & purification
  • Protein Kinase C / metabolism*
  • Skin / enzymology*
  • Structure-Activity Relationship


  • Acyl Coenzyme A
  • Diglycerides
  • Fatty Acids, Nonesterified
  • Phosphatidylserines
  • Phosphoproteins
  • Protein Kinase C
  • Calcium